Changes of microcirculation disturbance in model rat liver treated with Rougan Huaxian Granule

doi:10.3969/j.issn.2095-4344.0546

Abstract

Abstract:

BACKGROUND: Chinese herbal compound Rougan Huaxian Granule has been shown to improve chronic hepatitis and liver fibrosis. However, whether it can improve liver microcirculation in multi-path, multi-target and multiple-link remains unclear.
OBJECTIVE: To investigate the effects and differences of Rougan Huaxian Granule and its disassembled formulas on the regulation of microcirculation disturbance in model rat liver.
METHODS: The rat model of liver fibrosis was established by CCl4 compound factors. Four weeks later, the model rats were randomized into six groups: model group, Dahuang Zhechong Pill group, Rougan Huaxian Granule 1, 2, 3 and 4 groups, treated with Rougan Huaxian Granule, Bushen Yanggan Formula, Yiqi Jianpi Foamula and Huatan Jiedu Formula, Huoxue Huayu Formula combined with Ruanjian Sanjie Formula, respectively. The remaining normal rats were used as control group. The drug (0.1 mL/kg) was given via gavage, once daily for 12 weeks.
RESULTS AND CONCLUSION: Light microscopy showed that fibrous hyperplasia occurred in the liver mesenchyma, which divided the normal hepatic lobules into uneven cell masses (pseudolobule formation), suggesting the live fibrosis model was established successfully. Compared with the control group, the serum levels of NO and endothelin-1 were significantly increased in each group. With the progression of liver cirrhosis, the levels of NO and endothelin-1 were decreased significantly (P < 0.01), and the hepatic artery/vein activation time was shortened significantly (P < 0.05 or P < 0.01). Compared with the model group, the contents of NO and endothelin-1 in each treatment group were decreased in different degrees (P < 0.01), and the hepatic artery/vein activation time was prolonged (P < 0.01). Compared with Dahuang Zhechong Pill group, the contents of NO and endothelin-1 in Rougan Huaxian group 1 were significantly decreased (P < 0.05 or P < 0.01), and the hepatic vein activation time was prolonged (P < 0.01). In summary, the rat model of live fibrosis is successfully constructed. Rougan Huaxian Granule can promote the microcirculation of the liver and increase the hepatic microvascular flow rate, and delay the development of liver fibrosis. The mechanism may be related to the decrease in serum levels NO and endothelin-1.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Tissue Engineering, Liver Cirrhosis, Microcirculation, Models, Animal

CLC Number:

R452

Wei Dongjue1, Ye Dongmei2, Zhang Fengying1, Zhou Ying1, Wang Zhenchang3. Changes of microcirculation disturbance in model rat liver treated with Rougan Huaxian Granule [J]. Chinese Journal of Tissue Engineering Research, 2019, 23(3): 453-457.

Figures/Tables 2

2.1 实验动物数量分析大鼠120只，在第4周造模结束后随机麻醉处死8只，进入结果分析112只，无脱失值。 2.2 各组大鼠肝纤维化程度比较光学显微镜下观察正常对照组可见结构清晰完整的肝小叶和以静脉为中心向四周呈条索状放射排列的细胞(图1A)。模型组肝小叶结构紊乱，以分割、包绕肝小叶的粗大胶原纤维较为多见，伴随局部肝细胞严重的脂肪变性，部分细胞可见再生的肝细胞(双核) (图1B)，肝间质出现广泛纤维组织增生，将正常肝小叶分割成大小不等的肝细胞团(即假小叶形成)，说明模型构建成功。大黄蟅虫丸组与模型组比较，肝小叶结构破坏较模型组减轻，胶原沉淀减少，肝细胞水肿以及变性不如模型组明显。柔肝化纤颗粒组2，3与大黄蟅虫丸组情况相近。柔肝化纤颗粒组1与大黄蟅虫丸组相比，肝小叶结构较为完整，胶原纤维增生不多，炎细胞浸润较大黄蟅虫丸组少，肝细胞水肿以及变性情况较大黄蟅虫丸组改善明显(图1C)，见表1。 2.3 柔肝化纤颗粒对肝纤维化模型大鼠血清内皮素1及一氧化氮水平的影响见表2。与模型组和正常对照组比较，各给药组对内皮素1及一氧化氮的水平均有明显影响(P或P < 0.05)；其中柔肝化纤颗粒组1对大鼠血清内皮素1及一氧化氮的水平有明显的降低作用，并且跟大黄蟅虫丸组比较，内皮素1及一氧化氮的水平方面差异有显著性意义(P < 0.05)。 < 0.01 2.4 柔肝化纤颗粒对肝硬化大鼠超声造影检查结果的影响见表3。肝动脉始增时间仅在模型组与正常对照组比较有显著性意义(P < 0.05)，各组与正常对照组相比，肝静脉始增时间、肝动脉到肝静脉的渡越时间均有缩短(P < 0.01或P < 0.05)；各用药组与模型组相比，肝静脉始增时间、肝动脉"

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